Comprehensive Analysis of G-Quadruplexes in African Swine Fever Virus Genome Reveals Potential Antiviral Targets by G-Quadruplex Stabilizers

• DOI: 10.3389/fmicb.2021.798431
• Publication Date: 2021-12-16T19:01:06Z
• Authors: Elishiba Muturi; Fei Meng; Huan Liu; Mengwei Jiang; Hongping Wei; Hang Yang
• Keywords: G-quadruplex

African Swine Fever Virus (ASFV), a lethal hemorrhagic fever of the swine, poses major threat to world’s swine population and has so far resulted in devastating socio-economic consequences. The situation is further compounded by lack an approved vaccine or antiviral drug. Herein, we investigated novel anti-ASFV approach targeting G-Quadruplexes (G4s) viral genome. Bioinformatics analysis putative G-quadruplex-forming sequences (PQSs) genome ASFV BA71V strain revealed 317 PQSs on forward strand 322 reverse genome, translating density 3.82 PQSs/kb covering 9.52% entire which means that 85% genes have at least 1 PQS either strand. Biochemical characterization showed 8 out 13 conserved could form stable G4s presence K + , 4 them be stabilized G4 ligands, N-Methyl Mesoporphyrin (NMM), pyridostatin (PDS) vitro . An enhanced green fluorescent protein (EGFP)-based reporter system expression two G4-containing genes, i.e., P1192R D117L, significantly suppressed NMM PDS 293T cells. In addition, virus infection model inhibit replication Porcine Alveolar Macrophages (PAM) cells with EC 50 value 1.16 μM. Altogether, present study functional existent promoters, CDS, 3′ 5′ UTRs such as PDS, serve potential targets for antivirals.